It was once felt that a particular deletion of chromsome 16 described as del(16) or del(16)(q22) behaved as does inv(16) and t(16;16), but the trend in opinion today seems to discount this. It is possible that in some cases del(16) is favorable, but it is no longer considered a “favorable prognostic indicator” in and of itself as are inv(16) and t(16;16).

While these cytogenetic abnormalities can sometimes be found in almost any subtype of AML (FAB type), they tend to cluster characteristically within AML-M2 (in which most cases of t(8;21) are found) and AML-M4Eo (AML-M4 with eosinopohilia, where most cases of inversion 16 are found).

CBF AMLs were once felt to be highly sensitive to cytarabine (ara-c). Simply, the believe was that the leukemic cells would need a smaller amount of exposure to the chemotherapy in order to be killed off, allowing the chemotherapy to kill more cells, more quickly, throughout more of the body. It also was felt that this enhanced sensitivity helped overcome the rapid acquisition of resistance to chemotherapy that is a hallmark of AML, so that even as the cells began to become resistant they would have a bigger ‘cushion’ of heightened sensitivity. A CBF leukemia after a month of treatment might still be more sensitive to treatment than a non-CBF leukemia, even though both had acquired a degree of resistance.

However, later research has demonstrated that in the case of t(8;21) the leukemic cells may actually be less sensitive to cytarabine than are non-CBF leukemias. There is clearly a benefit to high-dose chemotherapy in t(8;21) leukemias as demonstrated statistically over and over, but what exactly the mechanism of action is remains unclear.

Heightened sensitivity to cytarabine in inv(16)/t(16;16) is still believed to be responsible for response in those CBF AMLs, and research in the lab has upheld this.

The recommended protocol after induction is a minimum of three courses of high-dose cytarabine. (HiDAC, preferably 3-gram HiDAC.) A fourth round is ideal, even a fifth if tolerable. There are variations on this theme in treating CBF AMLs, but all of these still revolve around the concept of numerous high doses of cytarabine. CBF AMLs have significantly better survival rates following these protocols than other AMLs.

Previously it was felt that AML-M3 had the best prognosis and response to treatment, but later research on CBF AMLs treated with multiple rounds of high-dose chemotherapy indicates that it is CBF AML that has the best prognosis, perhaps in part due to the much higher response to salvage therapy (therapy after a relapse) with inv(16)/t(16;16).

When people are told, “If you have to have an AML, this is the best type to have,” what is actually being referred to are the chances of having one of these favorable chromosomal abnormalities (which are what create/define a CBF AML) associated with a given subtype – not the subtype itself. (With the exception of AML-M3, which by definition involves a set of chromosomal abnormalities that creates a specific type of leukemia, although there are rare cases of AML-M3 that have different abnormalities and a different prognosis.)

Many people read or are told, for example, that AML-M4 is one of the best and most curable subtypes to have, but this really only applies to M4Eo with inversion 16. Unfortunately, without inversion 16 AML-M4 can present additional problems in that M4 (like M5, though not quite to the same degree) can be particularly invasive to the central nervous system (spine and brain), as well as other organs and tissues in general. M4 in the past was associated with a high rate of relapse from within the CNS, though with high-dose cytarabine and early prophylactic intrathecal chemotherapy the chances of this are small. (It’s not uncommon to find references in the literature to the idea that the consolidation chemotherapy of HiDAC alone – without intrathecal treatment, which in a nutshell is the injection of the chemotherapeutic drug directly into the spinal column – is enough to prevent CNS relapse on its own in a core binding factor AML.)

On prophylactic intrathecal chemotherapy: There is some debate over this in M4-Eo and M4 AML. Because high-dose cytarabine is the standard of treatment today, prophylactic intrathecal chemotherapy seems to be rather uncommon. It’s my opinion that anyone with M4 (and M5) should discuss at least having a lumbar puncture to test their spinal fluid for the presence of any cells. It is true that high-dose cytarabine likely deal with stray cells that have infiltrated the CNS, and there are risks to intrathecal chemotherapy just as there are to the rest of the chemotherapy regimen. And while a lumbar puncture is not pleasant, in skilled hands with sedation it should be far less traumatic than a bone marrow biopsy. But most importantly, a puncture can offer peace of mind either by demonstrating a lack of leukemic cells, or by locating them and initiating intrathecal chemotherapy. Some opinion discusses having a single round of intrathecal given at the same time the initial lumbar puncture for testing is performed. The risks of a CNS relapse – which I won’t go into here – far, far outweigh the risks and discomfort of a lumbar puncture and intrathecal chemo. I can see no reason to risk a CNS relapse or to risk a chance of missing CNS invasion given the stakes.